2018 Fiscal Year Research-status Report
Elucidation of in vivo protective effects of huntingtin-associated protein 1 against motor neuron degeneration.
| Project/Area Number |
18K15006
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| Research Institution | Yamaguchi University |
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Principal Investigator |
Md・Nabiul Islam 山口大学, 大学院医学系研究科, 助教 (80759671)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | HAP1 / Neurodegeneration / Motoneuron |
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| Outline of Annual Research Achievements |
We have reported previously that HAP1-expression is present in the sensory and autonomic neurons but absent in motor neurons of rat spinal cord, suggesting that the spinal motoneurons are, due to lack of putative HAP1 protectivity, more vulnerable to neurodegeneration. Since I am using transgenic and HAP1-Knockout mice in the present study, I have also examined the HAP1 expression in mouse spinal cord. It was found that there were no species differences in the expression of HAP1 in rodents. As it has not been clarified that the absence of HAP1-immunoreaction in the motor neurons is obvious or stage dependent, I am examining the complete profile of the HAP1-expression in the mouse spinal cord of embryonic and neonatal stages, which is under progress.
In addition to spinal cord, we have also examined the HAP1 expression in a cognitively important brain region, the retrosplenial-retrohippocampal area of brain in light of the relationship between neurodegenerative diseases. Here, HAP1-immunoreactive (ir) cells were classified into five groups: (1) a distinct retrosplenial cell cluster exclusive to the superficial layers of the granular cortex, (2) a thin line of cells in layers IV/V of the "subiculum-backing cortex," (3) cells associated with the medial entorhinal-subicular corner, (4) pericallosal cells, and (5) sporadic, widely-disseminated HAP1-immunoreactive cells. HAP1 may play an important role in protecting these cortical structures and functions for higher nervous activity by increasing the threshold to neurodegeneration and decreasing vulnerability to stress or aging.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
I have completed examining the distribution of HAP1 in the spinal cord of adult mice (from cervical to sacral level. Examining HAP1 immunoreaction in the embryonic and neonatal stages are progressing with good pace. We have also examining the HAP1 immunoreaction in the the retrosplenial-retrohippocampal area of brain in light of the relationship between neurodegenerative diseases. Here, HAP1-immunoreactive (ir) cells were classified into five groups suggesting the important role of HAP1 in protecting these cortical structures and functions for higher nervous activity by increasing the threshold to neurodegeneration and decreasing vulnerability to stress or aging. In this relation we have published research papers in different peer reviewed international journals. I have also presented my data related to this project in different national and international conferences.
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| Strategy for Future Research Activity |
To answer the question, whether the plausible HAP1 protection against in vivo motoneuron degeneration is stage dependent or not, a complete profile of the HAP1-expression in the spinal motor neurons of embryonic (ED15, ED 17, ED19), neonatal (day1, day 7), adult (10w), and aged (80w) mice of both sexes will be obtained using immunohistochemistry. Finally, to examine the protective functions of HAP1 from against neurodegeneration in vivo, we have generated motor neuron specific HAP1-transgenic (TG) mice. To clarify the protective functions of HAP1, I will perform a motor function-related behavioral test battery comparison between aged-wild type and aged-HAP1-TG mice, which includes locomotor activity test, hang test, paw print analysis, rotarod and grip strength test.
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| Causes of Carryover |
In the present study, I am using transgenic and knockout mice. There was a delay in getting genetically-modified mice due to the insufficient pregnancy rate of mice.
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Research Products
(9 results)
